Cell Biology of Membranes
Sommaire
The main feature of cellular architecture is the compartimentalization into distinct functional sub-cellular domains. Cellular membranes carry out highly specialized functions. Plasma membrane from neurones and muscle cells has domains that accumulate a set of specific proteins such as ionic channels, receptors and anchors for cytoskeleton fibers. The biogenesis and maintenance of those membrane sub-domains under normal or pathological conditions result from a complex interplay between gene expression, cell-to-cell interaction, signaling mechanisms, membrane traffic and cytoskeleton rearrangements. In the laboratory, we are interested in two topics: 1) differentiation of the neuromuscular junction (NMJ) and 2) cellular characterization of a group of neuromuscular disorders, the infantile spinal muscular atrophies (SMAs).
Figure 1: Putative role of membrane rafts in the actin-driven assembly of AChR clusters at the NMJ (from Stetzkowski-Marden et al., 2006)Aim N°1 (Jean Cartaud): How nicotinic acetylcholine receptors and associated molecules are recruited, assembled and stabilized in the postsynaptic membrane at the vertebrate neuromuscular junction is a key issue in synaptic differentiation. The current aim of our research is to unravel the cellular and molecular mechanisms involved in this processes. Recently, we demonstrated that sphingolipids/cholesterol-enriched lipid microdomains or lipid rafts are involved both in the intracellular transport and in the agrin-dependent assembly of AChR clusters. Our working hypothesis is that rafts represent signaling platforms for local nucleation of actin filaments ultimately leading to raft coalescence and AChR clustering (figure 1).
Figure 2: Localization of the SMN protein in the cytoplasm and in nuclear CBs.Aim N°2 (Suzie Lefebvre): The aim of our team is to unravel the cellular and molecular mechanisms involved in cell survival particularly in motoneuron degeneration observed in neuro-muscular disorders. The spinal muscular atrophy (SMA) gene product SMN protein is a key component in ribonucleoprotein (RNP) assembly. RNPs are involved in essential cellular functions, such as gene expression and its regulation. Accordingly, the ubiquitous SMN protein levels influence the composition of sub-cellular domains, including nuclear Cajal bodies (CBs). Understanding the mechanisms underlying physiological processes is also unravealing specific aspects of fundamental biology.
Sélection de publications
Renvoisé B, Colasse S, Burlet P, Viollet L, Meier UT, Lefebvre S.
The loss of the snoRNP chaperone Nopp140 from Cajal bodies of patient fibroblasts correlates with the severity of spinal muscular atrophy. Human Molecular Genetics (2009) 18 (7) : 1181-1189. Abstract
Bocquet N, Prado de Carvalho L, Cartaud J, Neyton J, Le Poupon C, Taly A, Grutter T, Changeux J P, Corringer P J.
A prokaryotic proton-gated ion channel from the nicotinic acetylcholine receptor family. Nature. 2007; 445: 116-9. Abstract
Renvoisé B, Khoobarry K, Gendron MC, Cibert C, Viollet L, Lefebvre S.
Distinct domains of the spinal muscular atrophy protein SMN are required for targeting to Cajal bodies in mammalian cells. Journal of Cell Sciences (2006) 119: 680-692. Abstract
Stetzkowski-Marden F, Gaus K, Recouvreur M, Cartaud A, Cartaud J.
Agrin elicits membrane lipid condensation at sites of acetylcholine receptor clusters in C2C12 myotubes. J Lipid Res. 2006; 47: 2121-33. Abstract
Marchand S, Devillers-Thiéry A, Pons S, Changeux JP, Cartaud J.
Rapsyn escorts the nicotinic acetylcholine receptor along the exocytic pathway via association with lipid rafts. J Neurosci. 2002; 22: 8891-901.
abstract
Last modified 03/14/2011